2-Decarboxy-2-hydroxymethyl-19,20-didehydro-PG1 compounds

ABSTRACT

The present invention provides novel 2-decarboxy-2-hydroxymethyl-19,20-didehydro-PG 1  compounds, methods for their preparation and pharmacological use for the induction of prostaglandin-like effect.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a division of Ser. No. 026,066, filed Apr. 2, 1979 pending issuance as a United States Patent.

BACKGROUND OF THE INVENTION

The present invention relates to novel prostaglandin analogs. Particularly, these compounds are analogs of the prostaglandins wherein the C-20-C-19 position is unsaturated. i.e., 19,20-didehydro-PG compounds. Most particularly, the present invention relates to novel 2-decarboxy-2-hydroxymethyl-19,20-didehydro-PG₁ compounds, a disclosure of the preparation and use of which is incorporated here by reference from U.S. Pat. No. 4,228,104.

Prior Art

Prostaglandin analogs exhibiting unsaturation in the C-17, C-18, or C-20 position are known in the art. See, for example, U.S. Pat. No. 3,919,285 German Offenlegungsschrift No. 2,635,985 (and its corresponding Derwent Farmdoc CPI No. 10302A), and U.S. Pat. No. 4,064,351 for examples of such compounds. See also the references cited in U.S. Ser. No. 026.066.

SUMMARY OF THE INVENTION

The present invention particularly provides:

A compound of the formula ##STR1## wherein D is (1) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,

(2) --(CH₂)₃ --CH₂ --CF₂ --,

(3) --(CH₂)₃ --O--CH₂ --,

(4) --(CH₂)₂ --O--(CH₂)₂ --,

(5) --CH₂ --O--(CH₂)₃ --, ##STR2## wherein g is zero, one, two, or three; wherein Q is ##STR3## wherein R₅ is hydrogen or methyl, wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl; wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;

wherein W is ##STR4## and wherein X is cis- or trans-CH═CH-- or --C.tbd.C--.

Specific embodiments of the present invention include

2-decarboxy-2-hydroxymethyl-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁α

2-decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁α

2-decarboxy-2-hydroxymethyl-11-deoxy-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-11-deoxy-16,16-dimethyl-19,20-didehydro-PGF.sub.1α,

2-decarboxy-2-hydroxymethyl-11-deoxy-16,16-difluoro-19,20-didehydro-PGF.sub.1α,

2-decarboxy-2-hydroxymethyl-11-deoxy-11.sub.α -hydroxymethyl-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-19,20-didehydro-PGF₁α,

2-decarboxy-2-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-11-deoxy-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-11-deoxy-16,16-dimethyl-19,20-didehydro-PGF.sub.1β,

2-decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁β,

2-decarboxy-2-hydroxymethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-dihydro-PGE₁,

2-decarboxy-2-hydroxymethyl-11-deoxy-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-11-deoxy-16,16-dimethyl-19,20-didehydro-PGE.sub.1,

2-decarboxy-2-hydroxymethyl-11-deoxy-16,16-difluoro-19,20-didehydro-PGE.sub.1,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-16,16-dimethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-16,16-difluoro-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-16,16-dimethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-16,16-difluoro-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGE₁,

2-decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGE₁.

The compounds of the present invention are particularly useful for inducing prostaglandin-like biological effects, as is described in U.S. Ser. No. 026,066. Uses of compounds in accordance with the present invention include, therefore, anti-asthmatic indication. 

I claim:
 1. A compound of the formula ##STR5## wherein D is (1) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,(2) --(CH₂)₃ --CH₂ --CF₂ --, (3) --(CH₂)₃ --O--CH₂ --, (4) --(CH₂)₂ --O--(CH₂)₂ --, (5) --CH₂ --O--(CH₂)₃ --, ##STR6## wherein g is zero, one, two, or three; wherein Q is ##STR7## wherein R₅ is hydrogen or methyl, wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl;wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; wherein W is ##STR8## and wherein X is cis- or trans-CH═CH-- or --C.tbd.C--.
 2. A compound according to claim 1, wherein D is -(CH₂)₃ -(CH₂)_(g) -CH₂ -, wherein g is zero, one, two or three.
 3. A compound according to claim 2, wherein g is one.
 4. A compound according to claim 3, wherein W is ##STR9##
 5. A compound according to claim 4, wherein R₂ is hydroxyl.
 6. A compound according to claim 5, wherein X is trans-CH═CH-.
 7. 2-Decarboxy-2-hydroxymethyl-19,20-didehydro-PGF₁α, a compound according to claim
 6. 8. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁α, a compound according to claim
 6. 9. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁α, a compound according to claim
 6. 10. A compound according to claim 4, wherein R₂ is hydrogen.
 11. A compound according to claim 10, wherein X is trans-CH═CH-.
 12. 2-Decarboxy-2-hydroxymethyl-11-deoxy-19,20-didehydro-PGF₁α, a compound according to claim
 11. 13. 2-Decarboxy-2-hydroxymethyl-11-deoxy-16,16-dimethyl-19,20-didehydro-PGF₁α, a compound according to claim
 11. 14. 2-Decarboxy-2-hydroxymethyl-11-deoxy-16,16-difluoro-19,20-didehydro-PGF₁α, a compound according to claim
 11. 15. A compound according to claim 4, where R₂ is hydroxymethyl.
 16. A compound according to claim 15, wherein X is trans-CH═CH-.
 17. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-19,20-didehydro-PGF₁α, a compound according to claim
 15. 18. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁α, a compound according to claim
 15. 19. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁α, a compound according to claim
 15. 20. A compound according to claim 3, wherein W is ##STR10##
 21. A compound according to claim 20, wherein R₂ is hydroxyl.
 22. A compound according to claim 21, wherein X is trans-CH═CH-.
 23. 2-Decarboxy-2-hydroxymethyl-19,20-didehydro-PGF₁β, a compound according to claim
 22. 24. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁β, a compound according to claim
 20. 25. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁β, a compound according to claim
 22. 26. A compound according to claim 20, wherein R₂ is hydrogen.
 27. A compound according to claim 26, wherein X is trans-CH═CH-.
 28. 2-Decarboxy-2-hydroxymethyl-11-deoxy-19,20-didehydro-PGF₁β, a compound according to claim
 27. 29. 2-Decarboxy-2-hydroxymethyl-11-deoxy-16,16-dimethyl-19,20-didehydro-PGF₁β, a compound according to claim
 27. 30. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁β, a compound according to claim
 27. 31. A compound according to claim 20, wherein R₂ is hydroxymethyl.
 32. A compound according to claim 31, wherein X is trans-CH═CH-.
 33. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-19,20-didehydro-PGF₁β, a compound according to claim
 32. 34. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGF₁β, a compound according to claim
 32. 35. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGF₁β, a compound according to claim
 32. 36. A compound according to claim 3, wherein W is ##STR11##
 37. A compound according to claim 36, wherein R₂ is hydroxyl.
 38. A compound according to claim 37, wherein X is trans-CH═CH-.
 39. 2-Decarboxy-2-hydroxymethyl-19,20-didehydro-PGE₁, a compound according to claim
 38. 40. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGE₁, a compound according to claim
 38. 41. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-19,20-dihydro-PGE₁, a compound according to claim
 38. 42. A compound according to claim 36, wherein R₂ is hydrogen.
 43. A compound according to claim 42, wherein X is trans-CH═CH-.
 44. 2-Decarboxy-2-hydroxymethyl-11-deoxy-19,20-didehydro-PGE₁, a compound according to claim
 43. 45. 2-Decarboxy-2-hydroxymethyl-11-deoxy-16,16-dimethyl-19,20-didehydro-PGE₁, a compound according to claim
 43. 46. 2-Decarboxy-2-hydroxymethyl-11-deoxy-16,16-difluoro-19,20-didehydro-PGE₁, a compound according to claim
 43. 47. A compound according to claim 36, wherein R₂ is hydroxymethyl.
 48. A compound according to claim 47, wherein X is trans-CH═CH-.
 49. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-19,20-didehydro-PGE₁, a compound according to claim
 48. 50. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-PGE₁, a compound according to claim
 48. 51. 2-Decarboxy-2-hydroxymethyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGE₁, a compound according to claim
 48. 52. A compound according to claim 3, wherein W is ##STR12##
 53. A compound according to claim 52, wherein R₂ is hydroxyl.
 54. A compound according to claim 53, wherein X is trans-CH═CH-.
 55. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-19,20-didehydro-PGE₁, a compound according to claim
 54. 56. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-16,16-dimethyl-19,20-didehydro-PGE₁, a compound according to claim
 54. 57. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-16,16-difluoro-19,20-didehydro-PGE₁, a compound according to claim
 54. 58. A compound according to claim 52, wherein R₂ is hydrogen.
 59. A compound according to claim 58, wherein X is trans-CH═CH-.
 60. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-19,20-didehydro-PGE₁, a compound according to claim
 59. 61. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-16,16-dimethyl-19,20-didehydro-PGE₁, a compound according to claim
 59. 62. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-16,16-difluoro-19,20-didehydro-PGE₁, a compound according to claim
 59. 63. A compound according to claim 52, wherein R₂ is hydroxymethyl.
 64. A compound according to claim 63, wherein X is trans-CH═CH-.
 65. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11.alpha.-hydroxymethyl-19,20-didehydro-PGE₁, a compound according to claim
 64. 66.2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19,20-didehydro-PGE₁, a compound according to claim
 64. 67. 2-Decarboxy-2-hydroxymethyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19,20-didehydro-PGE₁, a compound according to claim
 64. 